Orthopaedic surgeons vary in their surgical approaches to total knee arthroplasty. The aim of this investigation was to compare outcomes after two different surgical approaches. The study was a prospective single-centre longitudinal randomized controlled trial. A sub-vastus approach was compared with a medial para-patellar approach. Participating surgeons elected to randomize their patients to one of the two types of approach. Outcomes included the Knee Society (KS) Clinical Rating System, WOMAC Osteoarthritis Index, SF-36, and EuroQol (measured at 1, 6, 12 and 52 weeks post-operatively compared to baseline) complications, surgeon rated ease of exposure, and proportion of patients who had a lateral release. Two hundred and thirty one patients were randomized to the two approaches. One hundred and sixteen patients were randomized to the sub-vastus approach. At one week compared to baseline, range of motion, KS global, KS knee, and KS pain scores were significantly better in the sub-vastus group. At six weeks, the medial para-patellar group tended to have better outcomes, but not statistically significantly. At fifty-two weeks compared to baseline, the WOMAC global and pain scores, the SF36 physical function and role-physical scores, and the EuroQol utility and pain score were significantly better in the sub-vastus group. Surgeons reported the ease of exposure in the sub-vastus group was significantly worse on average. This trial is the largest of its kind to date, and the first, so far as we are aware, to compare clinical outcomes of different surgical approaches at one year post-operatively. The sub-vastus approach to total knee arthroplasty was more effective than a medial para-patellar approach at both one week and fifty-two weeks post-operatively in patients whose surgeons considered either approach would be suitable. However, surgeons reported worse ease of exposure in the sub-vastus group.